The human zeta gene has at least two positive regulatory elements with promoter-like activity. While the more 3' element initiates transcription in a tissue non-specific fashion, the upstream (5') element constitutes a novel core promoter that functions in a tissue-specific manner, with a 30 base pair region being sufficient for activity. Analysis of this region is remarkable for a stretch of 11 consecutive purines that are required for activity. Receptor engagement results in the phosphorylation of zeta on tyrosine, as well as the ubiquitination of zeta and other TCR components. Zeta is ubiquitinated on multiple intracellular lysine residues, and lysines placed in non-native positions also serve as substrates. Individual lysines can be covalently modified with a single ubiquitin moiety or with ubiquitin multimers. Receptor ubiquitination appears to be intimately associated with proximal events in T-cell activation as evidenced by its inhibition by herbimycin A, the loss of ubiquitination associated with Lck negative cell lines, and the enhanced ubiquitination seen with the tyrosine phosphatase inhibitor, pervanadate.